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英国弗朗西斯克里克研究所Axel Behrens、Rocio Sancho等研究人员合作发现，表达导管Ngn3的前体细胞有助于胰腺中成年β细胞的新生。2021年9月2日，国际知名学术期刊《细胞—干细胞》在线发表了这一成果。

通过结合系谱追踪、三维成像和单细胞RNA测序（scRNA-seq）方法，研究人员发现导管细胞随着时间的推移对β细胞群有贡献。使用Neurogenin3 (Ngn3)-CreERT系进行系谱追踪，研究人员发现表达内分泌核心转录因子Ngn3的导管细胞对δ细胞标记物体蛋白呈阳性，偶尔会共同表达胰岛素。Akita^+/-糖尿病小鼠中表达激素的导管细胞数量增加，Ngn3杂合子加速了糖尿病的发生。

Ngn3系谱追踪的胰岛细胞的scRNA-seq表明，导管衍生的表达生长抑素的细胞（其中一些保留了导管标记物的表达）产生了β细胞。这项研究确定了表达Ngn3的导管细胞是平衡和糖尿病中成人β细胞新生的来源，并表明除了β细胞增殖外，这一机制还维持着成人胰岛β细胞群。

据介绍，导管细胞被认为是成人β细胞新生的来源，但这一点仍有争议。

附：英文原文

Title: Ductal Ngn3-expressing progenitors contribute to adult β cell neogenesis in the pancreas

Author: Christopher Gribben, Christopher Lambert, Hendrik A. Messal, Ella-Louise Hubber, Chloe Rackham, Ian Evans, Harry Heimberg, Peter Jones, Rocio Sancho, Axel Behrens

Issue&Volume: 2021-09-02

Abstract: Ductal cells have been proposed as a source of adult β cell neogenesis, but this has remained controversial. By combining lineage tracing, 3D imaging, and single-cell RNA sequencing (scRNA-seq) approaches, we show that ductal cells contribute to the β cell population over time. Lineage tracing using the Neurogenin3 (Ngn3)-CreERT line identified ductal cells expressing the endocrine master transcription factor Ngn3 that were positive for the δ cell marker somatostatin and occasionally co-expressed insulin. The number of hormone-expressing ductal cells was increased in Akita+/ diabetic mice, and ngn3 heterozygosity accelerated diabetes onset. scRNA-seq of Ngn3 lineage-traced islet cells indicated that duct-derived somatostatin-expressing cells, some of which retained expression of ductal markers, gave rise to β cells. This study identified Ngn3-expressing ductal cells as a source of adult β cell neogenesis in homeostasis and diabetes, suggesting that this mechanism, in addition to β cell proliferation, maintains the adult islet β cell population.

DOI: 10.1016/j.stem.2021.08.003

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00340-4

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